Avermectins, a complex of related agents having antiparasitic activity, are known to be produced by aerobic fermentation of Streptomyces avermitilis strains ATCC 31267, 31271 and 31272 , e.g., U.S. Pat. Nos. 4,310,519 and 4,429,042. The last two strains cited represent a frozen vial and a lyophilized tube, respectively, of a culture obtained by ultraviolet irradiation of S. avermitilis ATCC No. 31267.
The strains of S. avermitilis cited in the above-mentioned U.S. patents produce a class of substances generically described as C-076 (avermectins, formula I below). The class comprises eight distinct but closely related compounds described as avermectin A1a, A1b, A2a, A2b, B1a, B1b, B2a and B2b. The "a" series of compounds refers to the natural avermectins wherein the 25-position substituent is (S)-sec-butyl, and the "b" series to those natural avermectins wherein the 25-position substituent is isopropyl. The designations "A" and "B" refer to avermectins wherein the 5-position substituent is methoxy or hydroxy, respectively. Lastly, the numeral "1" refers to avermectins wherein a double bond is present at the 22-23 position; and the numeral "2" refers to avermectins having a hydrogen at the 22-position and hydroxy at the 23-position.
Thus, the avermectins are compounds of formula I: ##STR1## wherein: the broken line indicates a single or a double bond;
R.sup.1 is hydroxy and is only present when said broken line is a single bond; PA1 R.sup.2 is isopropyl or sec-butyl; and PA1 R.sup.3 is methoxy or hydroxy.
Other strains of S. avermitilis are known to produce one or more known or "natural" avermectins, wherein the 25-position substituent is either isopropyl or (S)-sec-butyl(1-methylpropyl), or "non-natural" avermectins wherein the 25-position substituent is other than isopropyl or (S)-sec-butyl. For example, S. avermitilis ATCC 31780 is disclosed in U.S. Pat. No. 4,378,353; ATCC 53567 and ATCC 53568 are described in European Patent Application (EP) 276 131; ATCC 53692 is discussed in EP 276 103; and a description of NCIB 12121 is found in EP 214 731 However, each of these Streptomyces avermitilis strains are direct or indirect progeny of the S. avermitilis ATCC 31267 strain. Thus, the above-referenced S. avermitilis strains which are capable of producing one or more of the avermectin compounds only include the parent strain and its progeny.
One other S. avermitilis strain, ATCC 53814, has been described in the literature (U.S. Pat. No. 5,015,662). This strain has been distinguished by its ability to bioconvert a series of milbemycin-type compounds, and its inability to produce substantial quantities of avermectins.
The present invention provides a novel avermectin-producing strain, Streptomyces avermitilis subspecies niger NRRL 21005. The present invention further provides novel processes for the production of avermectins using Streptomyces avermitilis subspecies nger NRRL 21005.